Department of Pathology, Immunology and Laboratory Medicinehttps://pathology.ufl.edu
College of MedicineWed, 23 May 2018 19:53:02 +0000en-UShourly1https://wordpress.org/?v=4.9.6Dr. Timothy Garrett Examines New Approaches to Profiling Metabolomics and Translation to Clinical Analysis in Education Webinarhttps://pathology.ufl.edu/2018/05/17/dr-timothy-garrett-examines-new-approaches-to-profiling-metabolomics-and-translation-to-clinical-analysis-in-education-webinar/
Thu, 17 May 2018 15:19:46 +0000http://com-pathology.sites.medinfo.ufl.edu/?p=8219Measurement of metabolites represents the digital readout of health. A critical aspect of metabolomics is the utilization of high resolution mass spectrometric approaches to detect and identify metabolites from biological fluids and tissues.

The use of multi-analyte analyses, as well as high resolution mass spectrometric approaches, has the potential to transform clinical diagnostics for the next generation. This presentation will discuss profiling and quantitative metabolomics techniques such as traditional LC-MS based approaches and new methods that utilize direction analysis approaches.

In this webinar, which LabRoots will host June 29, attendees will gain a better understanding of the utilization of bioinformatic tools for interpreting results.

]]>Dr. Todd Brusko awarded for a three year project on Type 1 Diabeteshttps://pathology.ufl.edu/2018/04/30/dr-todd-brusko-awarded-for-a-three-year-project-on-type-1-diabetes/
Mon, 30 Apr 2018 20:25:59 +0000http://com-pathology.sites.medinfo.ufl.edu/?p=8187Dr. Todd Brusko, Associate Professor in the Experimental Pathology Division and Diabetes Institute at the University of Florida, was awarded $1.78M from the Leona & Harry Helmsley Charitable Trust for a three year project on Type 1 Diabetes.

Title: HUMAN ATLAS of NEONATAL DEVELOPMENT and EARLY LIFE-IMMUNITY (HANDEL-I)

The goal of this research is to elucidate immune system developmental over the first decade of life with a focus on immunologically active sites such as the bone marrow, thymus, lymphoid organs, and mucosal tissues. We hypothesize that early life events shape lymphocyte activation, differentiation, and compartmentalization in tissues and establish immune homeostasis or trigger autoimmunity, including T1D. The grant is based out of the University of Florida and conducted in collaboration with Dr. Donna Farber of Columbia University.

In a previous study, Dr. Morel showed that drugs that make less sugar available to immune cells could stop the development of lupus in a model of the disease. Sugar is important for many cell processes, so reducing the amount available has a similar effect as when a person eats less food—the cell’s activities slow down and it has less energy to fuel an attack. The same treatment also helped immune cells taken from the blood of people with lupus act more like healthy, non-lupus immune cells. Dr. Morel hopes that this treatment might help three existing drugs – belimumab, abatacept, and ruplizumab – that have small effects in people with lupus to work better. With support from her Novel Research Grant, she will test combinations of sugar-reducing drugs like metformin, a drug widely used in diabetes, with the three lupus treatments to see whether she can slow the disease or reverse kidney damage in lupus models.

What this study means for people with lupus

Dr. Morel is pursuing a highly promising translational research project aimed at treating lupus and its complications. Because she is working with drugs like metformin that are already approved for use in people, any positive results could be readily translated into clinical trials to test the efficacy of her drug combinations in people with lupus.

]]>Dr. Laurence Morel chosen as the 2018 UF College of Medicine Graduate Convocation Speakerhttps://pathology.ufl.edu/2018/03/23/dr-laurence-morel-chosen-as-the-2018-uf-college-of-medicine-graduate-convocation-speaker/
Fri, 23 Mar 2018 20:45:54 +0000http://com-pathology.sites.medinfo.ufl.edu/?p=8107Laurence Morel, PhD, Vice Chair for Research and Academic Affairs and Professor, will be the 2018 College of Medicine Graduate Convocation Speaker on Thursday, May 3rd, from 2-3pm with a reception to follow. The Graduate Student Organization student bod of the College of Medicine voted over the last few weeks and were of favor of Dr. Morel speaking. This is a highly significant honor reflecting Dr. Morel’s longstanding contributions and support of the students and program within the College of Medicine. Congratulations Dr. Morel!
]]>Congratulations to Jonathan Whittamore, PhD, of the Experimental Pathology Divisionhttps://pathology.ufl.edu/2018/03/21/congratulations-to-jonathan-whittamore-phd-of-the-experimental-pathology-division/
Wed, 21 Mar 2018 14:38:46 +0000http://com-pathology.sites.medinfo.ufl.edu/?p=8101Congratulations to Jonathan Whittamore, PhD, of the Experimental Pathology Division. He has recently received a research grant from the Oxalosis Hyperoxaluria Foundation. This award, entitled “The sulphate transporter SAT-1(SLC26a1) is essential for oxalate clearance from the liver in Primary Hyperoxaluria Type 1” and provides $200,000 of support for two years.

The vast majority of oxalate eliminated in the urine originates from liver metabolism. Hyperoxaluria (elevated urine oxalate) is a major risk factor for kidney stone formation, one of the most common forms of kidney disease for which treatment options are limited. While dietary sources of oxalate can be restricted, this cannot offset the continuous metabolic over-production by the Primary Hyperoxalurias (PHs), a group of rare inherited diseases caused by liver enzyme deficiencies. Of the three described forms, PH type 1 is the most frequently encountered and severe, resulting in recurrent kidney stone formation with progressive renal failure accompanied by widespread oxalate deposition in other organs (oxalosis), a further life-threatening complication. There has been considerable investment in understanding the metabolic pathways related to the PHs for the benefit of emerging and future treatment/curative options targeting the liver.

Remarkably, there is one critical aspect that has so far been completely overlooked – how the metabolic end-product oxalate is actually transported out of the liver into the blood. This is surprising considering the liver is the source of the overwhelming oxalate burden in PH1 patients and, incredibly, it is the one organ to not be afflicted by oxalosis. This means the cells of the liver possess an extremely efficient mechanism for eliminating oxalate, although this has not been systematically examined. The current model of liver oxalate transport is based on a very limited number of studies implicating a major role for a protein called SAT-1 (Sulfate Anion Transporter 1). It has been hypothesized that SAT-1 is upregulated in the PH1 liver but this notion remains untested. The goal of this proposal is to undertake the first systematic characterization of oxalate transport by the liver and formally test this hypothesis. This work is essential to a complete understanding of oxalate metabolism in PH1 and other forms of hyperoxaluria. Such basic information may prove beneficial for research into emerging and future treatment strategies, specifically those targeting the liver.

]]>New Article by Dr. David Ostrov – Genes and Autoimmune Diabeteshttps://pathology.ufl.edu/2018/02/23/new-article-by-dr-david-ostrov-genes-and-autoimmune-diabetes/
Fri, 23 Feb 2018 15:07:43 +0000http://com-pathology.sites.medinfo.ufl.edu/?p=8056Dr. David Ostrov, Associate Professor in the Experimental Pathology Division, has recently published an article in JCI (The Journal of Clinical Investigation).

Genes play a significant role in autoimmune diabetes. The genes most strongly associated with autoimmune diabetes produce a protein called HLA-DQ8 (HLA-DQ plays an important role in the immune system by stimulating T cells). In patients with autoimmune diabetes, HLA-DQ8 stimulates T cells that unfortunately recognize normal proteins such as insulin.

A drug capable of blocking the unwanted activity of HLA-DQ8 would be expected to prevent autoimmune diabetes in high-risk individuals (such as those inheriting HLA-DQ8), and also delay the progression of the disease in diabetes patients.

We identified a drug capable of binding HLA-DQ8 and blocking its unwanted activity (stimulating T cells). We used the crystal structure of HLA-DQ8 as the basis for screening 139,735 compounds by structure-based molecular docking using the University of Florida Research Computing Facility (HiPerGator#3 is the most powerful computer at a US Public University). We used a program developed by UCSF (called DOCK) to identify candidate compounds that were tested for activity on cells and in animals at the University of Colorado in the lab of Dr. Aaron Michels.

Dr. Michels conducted experiments showing that an approved orally deliverable drug blocked HLA-DQ8. Since this drug has been considered safe for more than 50 years (including usage in pregnant women), a clinical trial was approved and results from Dr. Michels’ Phase 1b diabetes prevention clinical trial at the University of Colorado, Denver will be reported in a new article in the JCI.

This study has significant implications for treatment of diabetes, and also other autoimmune diseases. This study suggests that the same approach (structure-based selection of drugs that bind HLA molecules) may be adapted to prevent autoimmune diseases such as rheumatoid arthritis, coeliac disease, multiple sclerosis, systemic lupus erythematosus and others.

]]>Faculty Awarded UF Term Professorshipshttps://pathology.ufl.edu/2017/09/15/faculty-awards/
Fri, 15 Sep 2017 16:23:27 +0000http://com-pathology.sites.medinfo.ufl.edu/?p=7557Congratulations to three Department of Pathology faculty who received UF Term Professorship Awards from the Dean of the College of Medicine and the Office of the Provost.

Given the clinically significant and serious consequences of elevated urinary oxalate concentrations that are associated with a number of diseases and conditions, there is still no effective pharmacological treatment to reduce urinary oxalate levels, which can lead to kidney stones, tissue deposition of oxalate salt and renal failure. While the principal route for oxalate excretion is the kidney, the intestine has been shown to make a substantial contribution to the enteric elimination, which should be exploited and not ignored. The studies proposed will specifically address a long-ignored gap in information about how these oxalate transport mechanisms, along the intestine, are regulated to coordinate the elimination of oxalate along the intestinal tract.

Please join us in congratulating Drs. Hatch and Whittamore on this exciting research opportunity.